According to the engineering requirements of multi-point flexible positioning of aircraft thin-walled parts in the assembly process, and based on the “N-2-1” positioning principle, this paper proposed a searching optimization algorithm to determine the selection of the number and layout of positioning points and the suction pressure while the thin-walled parts are on multi-point flexible positioning. Based on the analysis of the effects of associated parameters on positioning accuracy, and taking engineering requirements as the objective function and movement range of positioning points as constraints, the algorithm conducted distributed search and integrated optimization for the number and layout of positioning points and the suction pressure. In order to implement this algorithm, MATLAB was used as the main control loop program. The optimal choice of the number and layout of positioning points and the suction pressure was obtained by the combined calculation of MATLAB and ANSYS. The algorithm solved the problems of low efficiency and poor results of the conventional method which relied on operator experience or simply by virtue of the FEA software analysis. Finally, searching optimization calculations and experimental verification were proceeded for an engineering requirements. The numerical example and experimental results show that the algorithm has a strong engineering feasibility.